Suboptimal antiretroviral exposure is an important predictor of clinical outcome and may be due to incomplete adherence or pharmacokinetic variability. Alcohol is one of the most consistent predictors of non-adherence in resource rich-settings and is the drug of choice in resource-limited settings. Alcohol may also impact antiretroviral drug exposure through adherence and/or changes in CYP 3A metabolism of antiretroviral medications. Inadequate viral suppression through impaired adherence, treatment discontinuation/rationing, or pharmacokinetic alterations may lead to rapid viral resistance. While the predictors of adherence are well known in resource-rich settings, little is known about the correlates of adherence behavior in resource-limited settings, particularly sub-Saharan Africa. Less is known about the pharmacokinetics of generic antiretroviral therapy in African patients. There is no data on how alcohol may impact adherence, treatment duration, or pharmacokinetics and development of resistance in resource-limited settings. Since it is the most commonly abused substance in resource-limited settings, it is important to know how alcohol may impact these important treatment outcomes. We have developed valid and objective adherence measures in patients receiving HIV antiretroviral therapy in Kampala, Uganda, and we propose to recruit 174 patients in three alcohol strata to determine the impact of alcohol use on adherence and pharmacokinetics of generic Triomune (D4T/3TC/NVP) antiretroviral therapy over 12 months of observation. Triomune is an ideal medication to study adherence, may have important pharmacokinetic interactions with alcohol, and possesses an adherence resistance relationship not seen with other antiretrovirals. The specific aims of this study are to: 1) determine whether increased severity of alcohol use is associated with lower levels of adherence to and treatment interruptions/discontinuations of Triomune therapy, 2) determine the effect of alcohol use on pharmacokinetics of Triomune therapy, 3) determine the impact of alcohol use on HIV viral suppression mediated through adherence to and pharmac0kinetics of Triomune therapy, and 4) determine the impact of alcohol use on Triomune antiretroviral drug resistance mediated through adherence, treatment duration, and pharmacokinetics. This research will be an essential first step to determine the impact of alcohol on treatment outcomes to expanding antiretroviral therapy in sub-Saharan Africa.